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Biomedical subjects

J Correa

Publications and source records attributed to J Correa.

At least 19 recordsLinked to original sources

Safety, immunogenecity, and efficacy of an autoclaved Leishmania amazonensis vaccine plus BCG adjuvant against New World cutaneous leishmaniasis.

The safety, immunogenecity, and efficacy of two doses of an autoclaved-killed, whole cell Leishmania amazonensis vaccine (IFLA/BR/67/PH8) and BCG adjuvant (n = 750) against cutaneous leishmaniasis (CL) was compared with placebo (n = 756) in a randomized, placebo-controlled, blinded study. Systemic and local side-effects were more frequent in the vaccine than placebo group. Leishmanin skin test (LST) conversion was greater in the vaccine than placebo group 2 months after the second vaccination dose (74.4% versus 14.7%; P = 0.000001). The 26-month incidence of confirmed CL (n = 25) was similar between the vaccine (2.0%) and placebo groups (2.0% versus 1.3%; P > 0.05). LST conversion was not associated with CL protection and the vaccine did not offer significant protection against CL infection caused by L. Viannia spp. compared to placebo.

Adjuvants, Immunologic↗

Aerobic degradation of 2,4,6-TCP content in ECF bleached effluent.

Elemental chlorine-free (ECF) bleach effluents from kraft mill are characterised by: a chemical organic demand/biological organic demand (COD/BOD(5)) ratio of 4, chlorophenol content with low chlorine substitution, and toxicity. The effect of increasing the concentration of 2,4,6-trichlorophenol (2,4,6-TCP) content in ECF bleaching sequence effluent on the degradative activity of bacterial communities present in an aerobic system treatment was studied. An aerobic lagoon (AL) was used as a typical secondary treatment of kraft-mill effluent. AL displays a high performance of BOD(5) degradation (up to 90%); however, only 40% of the COD was removed. Simultaneously, the AL system shows a high ability to biodegrade 2,4,6-TCP up to 237 mg/l day. Kinetic parameters of the 2,4,6-TCP biodegradation by aerobic bacteria were determined. The K(s) and K(i) values were 34.3 and 50 mg/l 2,4,6-TCP, respectively. Moreover, the tolerance of aerobic bacteria was observed up to 1.3 g/l 2,4,6-TCP.

Bacteria, Aerobic↗

[Parasitic risks (bilharziosis and intestinal parasitosis) to Mboune's valley revitalisation (Senegal)].

In order to assess the parasitic risks related to M'Boune's valley water launching, a study has been carried out from September 16 to November 24, 1998 in 12 villages: four villages surrounding the Guiers lake, four villages surrounding Ferlo already water launched 10 years ago, and four villages within M'Boune not water launched. The prevalence rate of urinary bilharziosis is 0.002% in the frist area, 1.3% in the second one and 13.7% in the third area. In these areas, intestinal parasitosis are prevaling respectively at rates of 38.2%, 36.4% and 21.3%. Although, there is no reason to fear immediately a worsening of the epidemiological situation due to M'Boune's valley revitalisation project, nevertheless, appropriate steps should be taken right now aiming at tackling the extension of conditions related to hydric medium.

Adolescent↗

Evidence that the NH2 terminus of vph1p, an integral subunit of the V0 sector of the yeast V-ATPase, interacts directly with the Vma1p and Vma13p subunits of the V1 sector.

The vacuolar-type H(+)-ATPase (V-ATPase) is composed of a peripherally bound (V(1)) and a membrane-associated (V(0)) complex. V(1) ATP hydrolysis is thought to rotate a central stalk, which in turn, is hypothesized to drive V(0) proton translocation. Transduction of torque exerted by the rotating stalk on V(0) requires a fixed structural link (stator) between the complexes to prevent energy loss through futile rotation of V(1) relative to V(0); this work sought to identify stator components. The 95-kDa V-ATPase subunit, Vph1p, has a cytosolic NH(2) terminus (Nt-Vph1p) and a membrane-associated COOH terminus. Two-hybrid assays demonstrated that Nt-Vph1p interacts with the catalytic V(1) subunit, Vma1p. Co-immunoprecipitation of Vma1p with Nt-Vph1p confirmed the interaction. Expression of Nt-Vph1p in a Deltavph1 mutant was necessary to recruit Vma13p to V(1). Vma13p bound to Nt-Vph1p in vitro demonstrating direct interaction. Limited trypsin digests cleaves both Nt-Vph1p and Vma13p. The same tryptic treatment results in a loss of proton translocation while not reducing bafilomycin A(1)-sensitive ATP hydrolysis. Trypsin cleaved Vph1p at arginine 53. Elimination of the tryptic cleavage site by substitution of arginine 53 to serine partially protected vacuolar acidification from trypsin digestion. These results suggest that Vph1p may function as a component of a fixed structural link, or stator, coupling V(1) ATP hydrolysis to V(0) proton translocation.

Escherichia coli↗

Disruption and phenotypic analysis of six open reading frames from the left arm of Saccharomyces cerevisiae chromosome VII.

Six open reading frames (ORFs) from Saccharomyces cerevisiae chromosome VII were deleted using the kanMX4 module and the long-flanking homology-PCR replacement strategy in at least two different backgrounds. Among these ORFs, two of them (YGL100w and YGL094c) are now known genes which encode well-characterized proteins (Seh1p, a nuclear pore protein, and Pan2p, a component of Pab1p-stimulated poly(A) ribonuclease, respectively). The other four ORFs (YGL101w, YGL099w, YGL098w and YGL096w) code for proteins of unknown function, although the protein encoded by YGL101w has a strong similarity to the hypothetical protein Ybr242p. Gene disruptions were performed in diploid cells using the KanMX4 cassette, and the geneticin (G418)-resistant transformants were checked by PCR. Tetrad analysis of heterozygous deletant strains revealed that YGL098w is an essential gene for vegetative growth in three backgrounds, whereas the other five genes are non-essential, although we have found some phenotypes in one of them. YGL099wDelta strain did not grow at all at 15 degrees C and showed a highly impaired sporulation and a significantly lower mating efficiency. The other three deletants did not reveal any significant differences with respect to their parental strains in our basic phenotypic tests.

Chromosomes, Fungal↗

Substrate- and inhibitor-induced conformational changes in the yeast V-ATPase provide evidence for communication between the catalytic and proton-translocating sectors.

The vacuolar-type H(+)-ATPases (V-ATPases) are composed of two distinct sectors, a catalytic complex (V(1)) involved in ATP hydrolysis and a membrane-associated complex (V(0)) mediating proton translocation across a lipid bilayer. To date, little is known about the mechanism by which these two functions are coupled. We sought to examine the impact of nucleotide and cation binding on the structure of the core components of the catalytic complex and to determine whether conformational changes within the catalytic complex impact subunits of the membrane-associated complex. Nucleotide- and cation- induced changes in the catalytic core of the V-ATPase were investigated by monitoring changes in the rate and pattern of tryptic digests. ATP.Mg-induced changes were detected in both the catalytic (Vma1p or 69 kDa) and the regulatory subunits (Vma2p or 60 kDa) of the V(1) sector. ATP alone increased the rate of trypsinization of the regulatory subunit, but did not have any effect on Vma1p. Surprisingly, ATP also had an impact on the 95-kDa subunit, a component of the V(0) sector of the V-ATPase. Although the presence of divalent cations had no impact on the V(1) sector, the rate of trypsinization of the 95-kDa subunit was greatly enhanced. The effect of divalent cations on the structure of the 95-kDa subunit was abrogated when trypsinization was performed in the absence of the catalytic sector. Addition of bafilomycin A(1), a V-ATPase inhibitor that putatively binds to the 95-kDa subunit, increased the rate of trypsinization of the catalytic subunit. These data suggest that structural alterations within the V(1) sector result in alterations within the V(0) sector and vice versa. Clearly, a structural link must exist to couple the two sectors. The 95-kDa subunit is ideally suited to fulfill this role. Hydropathy analysis suggests a bipartite structure, with the NH(2)-terminal portion predicted to lie in an aqueous environment and the C-terminal portion predicted to contain 6 transmembrane segments. Tryptic digests of sealed vacuolar vesicles and immunofluorescence studies revealed that the large hydrophilic NH(2)-terminal domain of the 95-kDa subunit is localized toward the cytosol. This region therefore is ideally positioned to interact with components of the V(1) complex, potentially functioning as the elusive link between the two sectors of the V-ATPase.

Membrane Potentials↗

Sulfated Oligosaccharides Mediate the Interaction between a Marine Red Alga and Its Green Algal Pathogenic Endophyte.

The endophytic green alga Acrochaete operculata completely colonizes the sporophytes of the red alga Chondrus crispus; however, it does not penetrate beyond the outer cell layers of the gametophytes. Given that the life cycle phases of C. crispus differ in the sulfation pattern of their extracellular matrix carrageenans, we investigated whether carra-geenan fragments could modulate parasite virulence. lambda-Carrageenan oligosaccharides induced release of H(2)O(2), stimulated protein synthesis, increased carrageenolytic activity, and induced specific polypeptides in the pathogen, resulting in a marked increase in pathogenicity. In contrast, kappa-carrageenan oligosaccharides did not induce a marked release of H(2)O(2) from A. operculata but hindered amino acid uptake and enhanced their recognition by the host, resulting in a reduced virulence. Moreover, C. crispus life cycle phases were shown to behave differently in their response to challenge with cell-free extracts of A. operculata. Gametophytes exhibited a large burst of H(2)O(2), whereas only low levels were released from the sporophytes.

Journal Article↗

Grebe syndrome: clinical and radiographic findings in affected individuals and heterozygous carriers.

Grebe syndrome is a recessively inherited acromesomelic dysplasia. We studied, clinically and radiographically, 10 affected individuals, originating from Bahia, Brazil. The phenotype is characterized by a normal axial skeleton and severely shortened and deformed limbs, with a proximo-distal gradient of severity. The humeri and femora were relatively normal, the radii/ulnae and tibiae/fibulae were short and deformed, carpal and tarsal bones were fused, and several metacarpal and metatarsal bones were absent. The proximal and middle phalanges of the fingers and toes were invariably absent, while the distal phalanges were present. Postaxial polydactyly was found in several affected individuals. Several joints of the carpus, tarsus, hand, and foot were absent. Heterozygotes presented with a variety of skeletal manifestations including polydactyly, brachydactyly, hallux valgus, and metatarsus adductus. Grebe syndrome is caused by a missense mutation in the gene encoding cartilage-derived morphogenetic protein-1.

Abnormalities, Multiple↗

Anti-leishmanial IgE antibodies: a marker of active disease in visceral leishmaniasis.

Visceral leishmaniasis (VL) is characterized by a depression of the T helper cell type 1 immune response. Although mRNA expression for interleukin-4 (IL-4) is observed, evidence of the role of this cytokine in the pathogenesis of VL has been lacking. Since IL-4 is involved in IgE synthesis, we measured the total IgE and Leishmania antigen-specific IgE antibody levels in sera from patients with VL. Specific IgE antibodies detected by an ELISA technique after absorbing the sera with purified sheep IgG anti-human IgG were found in all 23 patients with VL and were not detected in subjects with subclinical Leishmania chagasi infection (n = 10), Chagas' disease (n = 10), atopic patients (n = 10), and healthy controls (n = 10). Levels of Leishmania-specific IgE (optical density values) before and after treatment were 0.100 +/- 0.03 (mean +/- SD) and 0.028 +/- 0.002, respectively (P < 0.05). These results indicate that a specific IgE response is useful in the diagnosis of active disease and to evaluate response to treatment.

Acute Disease↗

[Malaria lethality in Dakar pediatric environment: study of risk factors].

To determine risk factors for fatal malaria in Senegalese children, a 3-year case-control study was carried out between October 1992 and November 1995 at the Albert Royer Hospital in Dakar. The case group included 52 children who died from documented malaria in the hospital. The matched control group consisted of children who responded favorably to hospital treatment. Exposure to risk was measured with regard to age, nutritional status, educational level of parents, self-medication prior to hospitalization, socioeconomic level, degree of fever, and blood parasite levels. Cases and controls were compared using statistical tests for matched groups. Age lower than 5 years, poor educational level of parents, delay of treatment more than 24 hours, nutritional status, and blood parasite levels greater than 5% were associated with a significantly higher risk of fatal outcome. Conversely, low socio-economic level, recent self-medication, and fever over 41 degrees C were not associated with higher fatality. These findings emphasize the need for more information campaigns to encourage people to seek institutionalized care when fever appears. Our results also suggest that prophylactic treatment may be advisable in children under 5 years of age and in some high risk groups.

Adolescent↗

Overcoming prejudice.

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Acquired Immunodeficiency Syndrome↗

[Intestinal parasites in the vendors and consumers of street food. A study conducted in the Dakar area].

In order to assess the parasitic risk for street-food consumers, the authors conducted two studies from September to August 1996, one on street-food sellers (305) and the other on consumers (235). Among the consumers, 127 were considered as not exposed to risk, since they did not frequent the sector being surveyed, and 108 were exposed because they consumed at least one meal per day cooked by the sellers of this area. Both groups filled out a questionnaire and had their stools analysed according to the RITCHIE method. The infection rate was 60% among sellers and 45.5% among consumers. Protozoans were predominant in both groups. Among the consumers, those exposed were significantly more infected. Even though the sellers represent a parasitic risk due to their level of infection and the typology of parasites they shelter, one cannot assume that consumers are contaminated only by the sellers of street food. However, appropriate measures must be implemented in order to minimize risks for street-food consumers.

Feces↗

Catheter ablation of ventricular tachycardia in Chagasic Cardiomyopathy.

There is a limited experience with catheter ablation for treatment of ventricular tachycardia (VT) in Chagasic cardiomyopathy. A 30-year-old woman experienced episodes of palpitations and syncope due to attacks of VT. A diagnosis of Chagas disease was established on a biological basis. Two-dimensional echo and contrast ventriculography showed an apical aneurysm with thrombus. Surgery was indicated to resect the aneurysm and ablate the VT. Ventricular tachycardia recurred 1 month later despite therapy, including amiodarone. Two clinical frequent and well-tolerated tachycardias were identified. The site of origin was located in the right ventricular apex and in the apical-lateral wall of the left ventricle, respectively. Catheter ablation was performed at two sites with DC shocks (total energy 600 J) after unsuccessful radiofrequency ablation. Holter recordings performed during the post-operative period showed only infrequent extrasystoles. After follow-up of 24 months the patient remains asymptomatic. Drug-refractory VT in Chagasic cardiomyopathy can be ablated by medium-energy DC shocks after failure of radiofrequency ablation.

Adult↗

WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle's syndrome.

The amiloride-sensitive epithelial sodium channel (ENaC) plays a major role in sodium transport in kidney and other epithelia, and in regulating blood pressure. The channel is composed of three subunits (alphabetagamma) each containing two proline-rich sequences (P1 and P2) at its C-terminus. The P2 regions in human beta and gammaENaC, identical to the rat betagammarENaC, were recently shown to be deleted in patients with Liddle's syndrome (a hereditary form of hypertension), leading to hyperactivation of the channel. Using a yeast two-hybrid screen, we have now identified the rat homologue of Nedd4 (rNedd4) as the binding partner for the P2 regions of beta and gammarENaC. rNedd4 contains a Ca2+ lipid binding (CaLB or C2) domain, three WW domains and a ubiquitin ligase (Hect) domain. Our yeast two-hybrid and in vitro binding studies revealed that the rNedd4-WW domains mediate this association by binding to the P2 regions, which include the PY motifs (XPPXY) of either betarENaC (PPPNY) or gammarENaC (PPPRY). SH3 domains were unable to bind these sequences. Moreover, mutations to Ala of Pro616 or Tyr618 within the betarENaC P2 sequence (to PPANY or PPPNA, respectively), recently described in Liddle's patients, led to abrogation of rNedd4-WW binding. Nedd4-WW domains also bound to the proline-rich C-terminus (containing the sequence PPPAY) of alpharENaC, and endogenous Nedd4 co-immunoprecipitated with alpharENaC expressed in MDCK cells. These results demonstrate that the WW domains of rNedd4 bind to the PY motifs deleted from beta or gammaENaC in Liddle's syndrome patients, and suggest that Nedd4 may be a regulator (suppressor) of the epithelial Na+ channel.

Amino Acid Sequence↗